S Englander

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. pmc Protein folding and misfolding: mechanism and principles
    S Walter Englander
    The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia 19104 6059, USA
    Q Rev Biophys 40:287-326. 2007
  2. ncbi request reprint How cytochrome c folds, and why: submolecular foldon units and their stepwise sequential stabilization
    Haripada Maity
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    J Mol Biol 343:223-33. 2004
  3. pmc Protein structure change studied by hydrogen-deuterium exchange, functional labeling, and mass spectrometry
    Joan J Englander
    Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 100:7057-62. 2003
  4. pmc Cytochrome c folding pathway: kinetic native-state hydrogen exchange
    Linh Hoang
    The Johnson Research Foundation, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
    Proc Natl Acad Sci U S A 99:12173-8. 2002
  5. pmc Protein folding: the stepwise assembly of foldon units
    Haripada Maity
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
    Proc Natl Acad Sci U S A 102:4741-6. 2005
  6. ncbi request reprint Functional role of a protein foldon--an Omega-loop foldon controls the alkaline transition in ferricytochrome c
    Haripada Maity
    The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Proteins 63:349-55. 2006
  7. ncbi request reprint Order of steps in the cytochrome C folding pathway: evidence for a sequential stabilization mechanism
    Mallela M G Krishna
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, 19104 6059, USA
    J Mol Biol 359:1410-9. 2006
  8. pmc A unified mechanism for protein folding: predetermined pathways with optional errors
    Mallela M G Krishna
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6059, USA
    Protein Sci 16:449-64. 2007
  9. pmc Branching in the sequential folding pathway of cytochrome c
    Mallela M G Krishna
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6059, USA
    Protein Sci 16:1946-56. 2007
  10. pmc The foldon substructure of staphylococcal nuclease
    Sabrina Bedard
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
    J Mol Biol 376:1142-54. 2008

Research Grants

  1. Hydrogen exchange, proteins, and folding
    S Englander; Fiscal Year: 2005
  2. Hydrogen exchange, proteins, folding, and misfolding
    S Englander; Fiscal Year: 2007
  3. Protein dynamics studies by hydrogen exchange
    S Englander; Fiscal Year: 2007
  4. Hydrogen exchange, proteins, folding, and misfolding
    S Englander; Fiscal Year: 2009
  5. INTERMEDIATES AND THE BARRIERS IN PROTEIN FOLDING
    S Englander; Fiscal Year: 2001
  6. FUNCTIONAL LABELING OF CYTOCHROME C BY H-EXCHANGE & NMR
    S Englander; Fiscal Year: 1993
  7. Foldons, folding, and function
    S Walter Englander; Fiscal Year: 2010

Collaborators

Detail Information

Publications29

  1. pmc Protein folding and misfolding: mechanism and principles
    S Walter Englander
    The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia 19104 6059, USA
    Q Rev Biophys 40:287-326. 2007
    ..Cooperative native-like foldon units and the sequential stabilization process together generate predetermined stepwise pathways. Optional misfolding errors are responsible for 3-state and heterogeneous kinetic folding...
  2. ncbi request reprint How cytochrome c folds, and why: submolecular foldon units and their stepwise sequential stabilization
    Haripada Maity
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    J Mol Biol 343:223-33. 2004
    ..Much related information for Cyt c strongly conforms with this mechanism. Its generality is supported by available information for other proteins...
  3. pmc Protein structure change studied by hydrogen-deuterium exchange, functional labeling, and mass spectrometry
    Joan J Englander
    Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 100:7057-62. 2003
    ..Allosterically sensitive amide hydrogens located at near amino acid resolution help to confirm the reality of local unfolding reactions and their use to evaluate resolved structure changes in terms of allosteric free energy...
  4. pmc Cytochrome c folding pathway: kinetic native-state hydrogen exchange
    Linh Hoang
    The Johnson Research Foundation, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
    Proc Natl Acad Sci U S A 99:12173-8. 2002
    ..Four distinct unfolding steps are found to be kinetically ordered in the same pathway sequence inferred before...
  5. pmc Protein folding: the stepwise assembly of foldon units
    Haripada Maity
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
    Proc Natl Acad Sci U S A 102:4741-6. 2005
    ..Four other proteins have been found to show similar behavior. These results support stepwise protein folding pathways through discrete intermediates...
  6. ncbi request reprint Functional role of a protein foldon--an Omega-loop foldon controls the alkaline transition in ferricytochrome c
    Haripada Maity
    The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Proteins 63:349-55. 2006
    ..In addition, the results obtained confirm the epsilon-amino group of Lys79 and Lys73 as the alkaline replacement ligands and bear on the search for a triggering group...
  7. ncbi request reprint Order of steps in the cytochrome C folding pathway: evidence for a sequential stabilization mechanism
    Mallela M G Krishna
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, 19104 6059, USA
    J Mol Biol 359:1410-9. 2006
    ..Where the native structure of Cyt c requires sequential folding, in the first three steps, this is found. Where structural determination is ambiguous, in the final two steps, alternative parallel folding is found...
  8. pmc A unified mechanism for protein folding: predetermined pathways with optional errors
    Mallela M G Krishna
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6059, USA
    Protein Sci 16:449-64. 2007
    ..The integration of three well-documented principles in the PPOE model (cooperative foldons, sequential stabilization, optional errors) provides a unifying explanation for how proteins fold and why they fold in that way...
  9. pmc Branching in the sequential folding pathway of cytochrome c
    Mallela M G Krishna
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6059, USA
    Protein Sci 16:1946-56. 2007
    ....
  10. pmc The foldon substructure of staphylococcal nuclease
    Sabrina Bedard
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
    J Mol Biol 376:1142-54. 2008
    ..Because the unfolding parameters of many other residues are not determined, it seems likely that the concerted foldon units are more extensive than is shown by the 34 residues actually observed...
  11. pmc Protein folding: independent unrelated pathways or predetermined pathway with optional errors
    Sabrina Bedard
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 105:7182-7. 2008
    ..Structural, kinetic, and thermodynamic information for the folding intermediates and pathways of many proteins is consistent with the predetermined pathway-optional error (PPOE) model but contrary to the properties implied in IUP models...
  12. pmc Urea, but not guanidinium, destabilizes proteins by forming hydrogen bonds to the peptide group
    Woon Ki Lim
    Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 106:2595-600. 2009
    ..Results for guanidinium, however, are contrary to the expectation that it might H-bond. Evidently, urea and guanidinium, although structurally similar, denature proteins by different mechanisms...
  13. pmc The N-terminal to C-terminal motif in protein folding and function
    Mallela M G Krishna
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
    Proc Natl Acad Sci U S A 102:1053-8. 2005
    ..Possible reasons for this bias relate to the mechanisms for initial protein folding, native state stability, and final turnover...
  14. pmc Fast structural dynamics in reduced and oxidized cytochrome c
    Weixia Liu
    Department of Biochemistry and Biophysics, Johnson Research Foundation, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6059, USA
    Protein Sci 18:670-4. 2009
    ..The relative rigidity of both redox states also implies that dynamic relief of destructive electron transfer pathway interference is not operational in free cytochrome c...
  15. ncbi request reprint Recombinant equine cytochrome c in Escherichia coli: high-level expression, characterization, and folding and assembly mutants
    Jon N Rumbley
    The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6059, USA
    Biochemistry 41:13894-901. 2002
    ..In addition, destabilizing glycine mutants in the N-terminal helix are shown to affect the fractional yield of a heme inverted Cyt c isoform...
  16. ncbi request reprint Submolecular cooperativity produces multi-state protein unfolding and refolding
    S Walter Englander
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
    Biophys Chem 101:57-65. 2002
    ..Folding uses the same pathway in the reverse direction, moving from the unfolded to the native state through relatively discrete intermediate forms by the sequential addition of native-like secondary structural units...
  17. pmc Protein hydrogen exchange mechanism: local fluctuations
    Haripada Maity
    The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Protein Sci 12:153-60. 2003
    ..In both modes, ionic hydrogen exchange catalysts attack from the bulk solvent without diffusing through the protein matrix...
  18. ncbi request reprint Cooperative omega loops in cytochrome c: role in folding and function
    Mallela M G Krishna
    Department of Biochemistry and Biophysics, Johnson Research Foundation, University of Pennsylvania School of Medicine, 422 Curie Blvd, 1007 Stellar Chance Bldg, Philadelphia, PA 19104 6059, USA
    J Mol Biol 331:29-36. 2003
    ..This unit behavior accounts for an initial step on the unfolding pathway, a final step in refolding, and a number of other structural, functional and evolutionary properties...
  19. ncbi request reprint Folding units govern the cytochrome c alkaline transition
    Linh Hoang
    Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
    J Mol Biol 331:37-43. 2003
    ..These and other results show that the cooperative folding-unfolding behavior of protein foldons can account for a variety of functional activities in addition to determining folding pathways...
  20. ncbi request reprint Hydrogen exchange methods to study protein folding
    Mallela M G Krishna
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
    Methods 34:51-64. 2004
    ..The results obtained in these ways suggest principles that appear to explain the properties of partially folded intermediates and how they are organized into folding pathways. The application of these methods is detailed here...
  21. pmc Backbone and side-chain heteronuclear resonance assignments and hyperfine NMR shifts in horse cytochrome c
    Weixia Liu
    Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Protein Sci 12:2104-8. 2003
    ..The refined g-tensors were then used to probe for redox-dependent structure change in the two proteins...
  22. ncbi request reprint Intimate view of a kinetic protein folding intermediate: residue-resolved structure, interactions, stability, folding and unfolding rates, homogeneity
    Mallela M G Krishna
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
    J Mol Biol 334:501-13. 2003
    ..The general problem of homogeneous versus heterogeneous intermediates and pathways is discussed...
  23. ncbi request reprint Protein misfolding: optional barriers, misfolded intermediates, and pathway heterogeneity
    Mallela M G Krishna
    Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
    J Mol Biol 343:1095-109. 2004
    ..Related observations for other proteins (partially misfolded intermediates, pathway heterogeneity) might be similarly explained in terms of the optional insertion of error-dependent barriers into a classical folding pathway...
  24. pmc Hydrogen exchange and mass spectrometry: A historical perspective
    S Walter Englander
    The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6059, USA
    J Am Soc Mass Spectrom 17:1481-9. 2006
    ..This article briefly reviews the advances that have led us to this point and the understanding that has so far been achieved...
  25. pmc The Mad2 partial unfolding model: regulating mitosis through Mad2 conformational switching
    John J Skinner
    Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Cell Biol 183:761-8. 2008
    ..Recent structural, biochemical, and cell biological advances suggest that the catalyzed conversion of Mad2 requires a major structural rearrangement that transits through a partially unfolded intermediate...
  26. pmc Structure and properties of alpha-synuclein and other amyloids determined at the amino acid level
    Charyl Del Mar
    The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 102:15477-82. 2005
    ..Seeding specificity, strain variability, and species barriers then arise because newly added parallel in-register chains must faithfully reproduce the same set of adaptations...
  27. ncbi request reprint Fast and slow intermediate accumulation and the initial barrier mechanism in protein folding
    Bryan A Krantz
    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA
    J Mol Biol 324:359-71. 2002
    ..Results available provide little support for early intermediate accumulation before an initial search-dependent nucleation barrier...
  28. pmc Folding trajectories of human dihydrofolate reductase inside the GroEL GroES chaperonin cavity and free in solution
    Reto Horst
    Department of Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 104:20788-92. 2007
    ....
  29. ncbi request reprint The E46K mutation in alpha-synuclein increases amyloid fibril formation
    Eric A Greenbaum
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 280:7800-7. 2005
    ..These findings support the notion that aberrant alpha-synuclein polymerization resulting in the formation of pathological inclusions can lead to disease...

Research Grants31

  1. Hydrogen exchange, proteins, and folding
    S Englander; Fiscal Year: 2005
    ..An approach will be attempted that promises to make the native state HX method generally applicable to the majority of proteins which have so far not been accessible to this analysis. Other work is planned. ..
  2. Hydrogen exchange, proteins, folding, and misfolding
    S Englander; Fiscal Year: 2007
    ....
  3. Protein dynamics studies by hydrogen exchange
    S Englander; Fiscal Year: 2007
    ..To study the functional role of the dynamic dimension of protein structure, hydrogen exchange approaches will be applied to the study of enzymatic function. ..
  4. Hydrogen exchange, proteins, folding, and misfolding
    S Englander; Fiscal Year: 2009
    ..abstract_text> ..
  5. INTERMEDIATES AND THE BARRIERS IN PROTEIN FOLDING
    S Englander; Fiscal Year: 2001
    ..The experiments will use mammalian, bacterial, and genetically engineered versions of cytochrome c as model proteins, and other useful model proteins. ..
  6. FUNCTIONAL LABELING OF CYTOCHROME C BY H-EXCHANGE & NMR
    S Englander; Fiscal Year: 1993
    ....
  7. Foldons, folding, and function
    S Walter Englander; Fiscal Year: 2010
    ....